Neural response to working memory load varies by dopamine transporter genotype in children

Abstract

Inheriting two (10/10) relative to one (9/10) copy of the 10-repeat allele of the dopamine transporter genotype (DAT1) is associated with Attention Deficit Hyperactivity Disorder, a childhood disorder marked by poor executive function. We examined whether functional anatomy underlying working memory, a component process of executive function, differed by DAT1 in 7-12 year-old typically developing children. 10/10 and 9/10 carriers performed a verbal n-back task in two functional magnetic resonance imaging (fMRI) runs varying in working memory load, high (2-back vs. 1-back) and low (1-back vs. 0-back). Performance accuracy was superior in 9/10 than 10/10 carriers in the high but not low load runs. Examination of each run separately revealed that frontal-striatal-parietal regions were more activated in 9/10 than 10/10 carriers in the high load run; the groups did not differ in the low load run. Examination of load effects revealed a DAT1xLoad interaction in the right hemisphere in the caudate, our a priori region of interest. Exploratory analysis at a more liberal threshold revealed this interaction in other basal ganglia regions (putamen, and substantial nigra/subthalamic nuclei - SN/STN) and in medial parietal cortex (left precuneus). The striatal and parietal regions were more activated in 9/10 carriers under high than low load, and DAT1 differences (9/10>10/10) were evident only under high load. In contrast, SN/STN tended to be more activated in 10/10 carriers under low than high load and DAT1 differences (10/10>9/10) were evident only under low load. Thus, 10-repeat homozygosity of DAT1 was associated with reduced performance and a lack of increased basal ganglia involvement under higher working memory demands.

Copyright 2010 Elsevier Inc. All rights reserved.

Figures

Figure 1

Interaction between DAT1 (9/10, 10/10) and working memory load (High WM Run, Low WM Run) in right caudate (y=1), p < .05 FWE corrected for small volume. Graph shows mean contrast estimates (± standard error) in the activated cluster by DAT1 and working memory load (* p < .01).

Figure 2

Regions showing the interaction of DAT1 (9/10, 10/10) and working memory load (High WM Run, Low WM Run) in whole brain analysis (p < 0.005 uncorrected, extent threshold 5 voxels). Graph shows mean contrast estimates (± standard error) for each activated cluster by DAT1 and load (*p < .05).